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Int J Mol Sci
2023 Sep 12;2418:. doi: 10.3390/ijms241813985.
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Amphibian-Derived Natural Anticancer Peptides and Proteins: Mechanism of Action, Application Strategies, and Prospects.
Chen Q
,
Wu J
,
Li X
,
Ye Z
,
Yang H
,
Mu L
.
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Cancer is one of the major diseases that seriously threaten human life. Traditional anticancer therapies have achieved remarkable efficacy but have also some unavoidable side effects. Therefore, more and more research focuses on highly effective and less-toxic anticancer substances of natural origin. Amphibian skin is rich in active substances such as biogenic amines, alkaloids, alcohols, esters, peptides, and proteins, which play a role in various aspects such as anti-inflammatory, immunomodulatory, and anticancer functions, and are one of the critical sources of anticancer substances. Currently, a range of natural anticancer substances are known from various amphibians. This paper aims to review the physicochemical properties, anticancer mechanisms, and potential applications of these peptides and proteins to advance the identification and therapeutic use of natural anticancer agents.
Figure 1. The structure of the main active ingredient in HuaChansu. (Structural formulae from the website: https://pubchem.ncbi.nlm.nih.gov/, accessed on 16 July 2023).
Figure 2. Membrane cleavage of natural anticancer peptides of amphibian origin.
Temporin1CEa is a peptide used by the host to defend against pathogens. It is derived from the skin secretion of the Chinese brown frog (Rana chensinensis). When incubated with breast cancer cells at a specific concentration, it causes a loss of membrane symmetry and integrity, leading to a decrease in cell vitality [47]. A similar effect has been observed in melanoma. In fact, studies have shown that human A375 melanoma cells express 50 times more PS than non-cancerous HaCaT cells. As a result, Temporin1CE can bind to PS with high affinity, causing cytotoxicity [48]. Anionic anticancer peptides have also been found to have anticancer effects through direct membrane lysis. Maximin H5 is the first anionic amphibian-derived anticancer peptide demonstrating anticancer activity. After deamination of its C-terminus, Maximin H5 exhibits a lower level of an α-helical structure while penetrating glioma cell membranes, which suggests that the terminal amide group of Maximin H5 is necessary for its membrane-lytic and anticancer activities [49]. Other anticancer peptides with similar functions include citropin 1.1 from the tree frog Litoria citropa [50], aurein 1.2 from Litoria raniformis [15], and Magainins from Xenopus laevis [51] (Table 2).
Figure 3. Mechanism of action of natural anticancer peptides and proteins of amphibian origin.
Figure 4. Combination strategies of natural anticancer peptides and proteins.